An attribute that many organisms, including humans, possess is memory of past events. This attribute has been studied for many decades with much information now available that explains many of its ramifications. For example, two basic types of memory have been identified: transcription-independent memory, which includes short term memory, and transcription-dependent memory, which includes long term memory.
Gpr12 is an orphan GPCR. Analysis of Gpr12 expression by in situ hybridization revealed that Gpr12 is widely expressed in the mouse CNS, with highest levels of expression within hippocampus and thalamus. (Ignatov et al., 2003, J. Neurosci. 23:907-914). The endogenous ligand of Gpr12 is unknown. Phylogenetic analysis of Gpr12 revealed the orphan receptors Gpr3 and Gpr6 as closest homologous of Gpr12. The subgroup comprising the three orphan GPCRs is most closely related to the Mcr (melanocortin-like peptide) and Edg (endothelial differentiation) families of GPCRs. This indicates lipids or peptides as possible ligand for Gpr12. Sphingosylphosphorylcholine (SPC) activates Gpr12 in heterologous expression systems. SPC promotes differentiation and maturation of cultured embryonic cortical neurons Id. However the endogenous ligand of Gpr12 and its in vivo function in the adult CNS are unknown.
Previous results showed that Gpr12 signals via a Gαi dependent mechanism. Id. The cAMP/PKA pathway regulates CREB activity and long-term memory in the mammalian brain (Abel et al., 1997, Cell 88:615-626), (Bourtchouladze et al., 1998, Learn Mem. 5:365-374), (Barad et al., 1998, Proc. Natl. Acad. Sci USA 95:15020-15025), (Bourtchouladze et al., 2003, Proc. Natl. Acad. Sci USA 100:10518-10522).